Journal Article

Antimalarial drug resistance in the Central and Adamawa regions of Cameroon: Prevalence of mutations in P. falciparum crt, Pfmdr1, Pfdhfr and Pfdhps genes

Tuedom, Aline Gaelle Bouopda, Sarah-Matio, Elangwe Milo, Ayong, Lawrence, Feufack-Donfack, Brice Lionel, Abate, Luc, Bayibeki, Albert Ngano, Morlais, Isabelle, Awono-Ambene, Hermann Parfait, Moukoko, Carole Else Eboumbou, Berry, Antoine, Nsango, Sandrine Eveline, Maffo, Christelle Ngou

2021

Overview

The spread of Plasmodium falciparum resistant parasites remains one of the major challenges for malaria control and elimination in Sub Saharan Africa. Monitoring of molecular markers conferring resistance to different antimalarials is important to track the spread of resistant parasites and to optimize the therapeutic lifespan of current drugs. This study aimed to evaluate the prevalence of known mutations in the drug resistance genes Pfcrt , Pfmdr1 , Pfdhfr and Pfdhps in two different epidemiological settings in Cameroon. Dried blood spots collected in 2018 and 2019 from asymptomatic individuals were used for DNA extraction and then the Plasmodium infection status was determined byPCR. Detection of SNPs was performed by nested PCR followed by allele-specific restriction analysis (ASRA). The prevalence of each genotype was compared between sites using the Chi square and Fisher’s exact tests. A high prevalence of the Pfcrt K76 wild type allele was found in both sites (88.5 and 62.29% respectively; P< 0,0001). The prevalence of Pfmdr1 mutations 86Y and 1246Y was respectively 55.83 and 1.45% in Mfou and 45.87 and 5.97% in Tibati, with significant difference between the studied areas (P<0.0001). Overall, the Pfdhfr triple-mutant genotype (51I/59R/108N) was highly prevalent (> 96%), however no SNP was detected at codon 164. In Pfdhps , the prevalence of the 437G mutation reached (90%) and was at higher frequency in Mfou (P< 0.0001). Overall, the Pfdhps mutations 540E and 581G were less common (0.33 and 3.26%, respectively). The quadruple resistant genotype ( Pfdhfr 51I/59R/108N+ Pfdhp 437G) was found almost 90% of the samples. The wild-type genotype ( Pfdhfr N51/C59/S108/164I+ Pfdhps A437/K540/A581) was never identified and the sextuple mutant ( Pfdhfr 51I/59R/108N+ Pfdhp 437G/540E/581G), kwon as super resistant appeared in two samples from Tibati. These findings demonstrate declining trends in the prevalence of mutations conferring resistance to 4-aminoquinolines, especially to chloroquine. However, a high level of mutations in P . falciparum genes related to SP resistance was detected and this raises concerns about the future efficacy of IPTp-SP and SMC in Cameroon.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adolescent / Adult / Antimalarials - pharmacology / Antimalarials - therapeutic use / Biology and Life Sciences / Cameroon - epidemiology / Child / Dihydropteroate Synthase - genetics / Drug Resistance - genetics / Drug resistance in microorganisms / Female / Gene mutations / Genetic aspects / Genotype / Human health and pathology / Humans / Infectious diseases / Life Sciences / Malaria, Falciparum - drug therapy / Malaria, Falciparum - epidemiology / Malaria, Falciparum - parasitology / Male / Medicine and Health Sciences / Membrane Transport Proteins - genetics / Multidrug Resistance-Associated Proteins - genetics / Mutation / Parasitological research / People and Places / Plasmodium falciparum / Plasmodium falciparum - drug effects / Plasmodium falciparum - genetics / Polymorphism, Single Nucleotide / Prevalence / Protozoan Proteins - genetics / Statistics / Tetrahydrofolate Dehydrogenase - genetics